The aging immune system (immunosenescence) has been implicated with increased morbidity and mortality in the elderly. Of note, T cell aging and low-grade inflammation (inflammaging) are implicated with several age-related conditions. The expansion of late-differentiated T cells (CD28 −), regulatory T cells, increased serum levels of autoantibodies, and pro-inflammatory cytokines were implicated with morbidities during aging. Features of accelerated immunosenescence can be identified in adults with chronic inflammatory conditions, such as rheumatoid arthritis, and are predictive of poor clinical outcomes. Therefore, there is an interplay between immunosenescence and age-related diseases. In this review, we discuss how the aging immune system may contribute to the development and clinical course of age-related diseases such as neurodegenerative diseases, rheumatoid arthritis, cancer, cardiovascular, and metabolic diseases.

Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV) is the most common respiratory illness in children in the first year of life. RSV bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. Neutrophils and their products are present in the airways of RSV-infected patients who developed increased lung disease. Neutrophil Extracellular Traps (NETs) are formed by the release of granular and nuclear contents of neutrophils in the extracellular space in response to different stimuli and recent studies have proposed a role for NETs in viral infections. In this study, we show that RSV particles and RSV Fusion protein were both capable of inducing NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET release in a concentration-dependent fashion with both neutrophil elastase and myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled by DNase treatment, confirming that their backbone is chromatin. This viral protein caused the release of extracellular DNA dependent on TLR-4 activation, NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation. Together, these results demonstrate a coordinated signaling pathway activated by F protein that led to NET production. The massive production of NETs in RSV infection could aggravate the inflammatory symptoms of the infection in young children and babies. We propose that targeting the binding of TLR-4 by F protein could potentially lead to novel therapeutic approaches to help control RSV-induced inflammatory consequences and pathology of viral bronchiolitis.

Neutrophil extracellular traps (NETs) are a combination of DNA fibers and granular proteins, such as neutrophil elastase (NE). NETs are released in the extracellular space in response to different stimuli. Carrageenan is a sulfated polysaccharide extracted from Chondrus crispus, a marine algae, used for decades in research for its potential to induce inflammation in different animal models. In this study, we show for the first time that carrageenan injection can induce NET release in a mouse model of acute peritonitis. Carrageenan induced NET release by viable neutrophils with NE and myeloperoxidase (MPO) expressed on DNA fibers. Furthermore, although this polysaccharide was able to stimulate reactive oxygen species (ROS) generation by peritoneal neutrophils, NADPH oxidase derived ROS were dispensable for NET formation by carrageenan. In conclusion, our results show that carrageenan-induced inflammation in the peritoneum of mice can induce NET formation in an ROS-independent manner. These results may add important information to the field of inflammation and potentially lead to novel anti-inflammatory agents targeting the production of NETs.Keywords: Carrageenan r Myeloperoxidase r Neutrophil Elastase r Neutrophil Extracellular Traps r Neutrophils Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNeutrophils are the first cells involved in defense against pathogens and present a mechanism called neutrophil extracellular traps (NETs), which are extracellular structures able to trap and kill pathogens [1,2]. NETs are fibers made of Correspondence: Prof. Márcio V. F. Donadio e-mail: mdonadio@pucrs.br decondensed chromatin (histones and DNA) decorated with antimicrobial proteolytic enzymes present in the granules of neutrophils (such as neutrophil elastase (NE) and myeloperoxidase (MPO)) [3] and other nuclear components, all apparently involved in its mechanism of action [4]. There are a variety of stimuli yet described in the literature including proteins, bacteria, fungi, viruses, and cytokines capable of inducing NETs release [1,[5][6][7]. NETs are present in a plenty of in vivo inflammatory conditions, such as endometriosis [8] importance of exploring inflammatory stimuli involved in NETs formation.Carrageenan is a sulfated polysaccharide extracted from Chondrus crispus, a marine algae, used for decades in research for its potential to induce inflammation [13]. Also, carrageenan is widely used by the food industry as a gelling agent [13]. Due to the potential induction of inflammation, carrageenan is often used as a model of pleurisy [14,15], peritonitis [16,17], and edema [17,18] in experimental animals. The injection of carrageenan triggers an acute inflammation associated with hyperalgesy, which is characterized by edema and an exacerbated response to thermal and mechanical stimuli [13]. Bhattacharyya and colleagues found that carrageenan-induced inflammation in vitro in human colonocytes occurs through activation of Tolllike receptor...

No abstract

The aim of this study is to evaluate the response to an inflammatory stimulus in mice exposed to LPS-induced neonatal stress at different ages and sexes. Balb/c mice were submitted to intraperitoneal injections on postnatal days 3 and 10 with lipopolysaccharide (nLPS) or saline solution (nSal). At 21 or 60 days, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species, and neutrophil extracellular traps (NETs) production were measured in peritoneal fluid. LPS-induced neonatal stress can reduce inflammatory cytokines in males and females. An increase in NETs production was observed when 60 day nLPS animals were compared to 21 day mice in both sexes. The ROS production was not affected by neonatal stress. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a sex-dependent effect. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 600-613, 2016.

Background: Cocaine use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of Neutrophil Extracellular Traps (NETs) and related intracellular signaling. We also investigated the role of early-life stress in inflammatory profiles. Methods: Blood samples, clinical, data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HC). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular ROS generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. Results: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared with HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signaling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. Conclusion: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.